title: Anxiety-associated alternative polyadenylation of the serotonin transporter mRNA confers translational regulation by hnRNPK.
abstract: The serotonin transporter (SERT) is a major regulator of serotonergic neurotransmission and anxiety-related behaviors. SERT is expressed in two alternative polyadenylation forms that differ by an evolutionarily conserved element in the 3' untranslated region of its mRNA. Expression of SERT mRNA containing the distal polyadenylation element is associated with decreased anxiety-related behaviors in mice and humans, suggesting that this element has behaviorally relevant modulatory effects on SERT expression. We have identified heterogeneous nuclear ribonucleoprotein K (hnRNPK), a protein known to integrate multiple signal transduction pathways with gene expression, as a SERT distal polyadenylation element binding protein. This interaction is functionally meaningful because genetic manipulation of hnRNPK alters expression of the SERT protein. Furthermore, the trophic factor S100β induces Src-family kinase-mediated tyrosine phosphorylation of hnRNPK and increased SERT expression. These results identify a previously unknown mechanism of regulated SERT expression and provide a putative mechanism by which the SERT distal polyadenylation element modulates anxiety-related behaviors.
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA. yoy2004@med.cornell.edu
authors.forename: YoneJung
authors.initials: Y
authors.lastname: Yoon
authors.forename: Morgan C
authors.initials: MC
authors.lastname: McKenna
authors.forename: David A
authors.initials: DA
authors.lastname: Rollins
authors.forename: Minseok
authors.initials: M
authors.lastname: Song
authors.forename: Tal
authors.initials: T
authors.lastname: Nuriel
authors.forename: Steven S
authors.initials: SS
authors.lastname: Gross
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Glatt
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D010766:Phosphorylation; D011061:Poly A / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C072074:HNRNPK protein, human; D011061:Poly A; D019061:src-Family Kinases